Characterization of breast tumors with unbalanced levels of progesterone receptor isoforms: a proteomic approach

Autores
Elia, Andres Maximiliano; Sánchez, Jana; Vitorino, Rui; Saldain, Leo; Martínez Vazquez, Paula; Burruchaga, Javier; Spengler, Eunice; Muñoz, Javier; Rojas, Paola Andrea; Helguero, Luisa; Lanari, Claudia Lee Malvina
Año de publicación
2022
Idioma
inglés
Tipo de recurso
documento de conferencia
Estado
versión publicada
Descripción
It is well established that progesterone receptors (PR) play a relevant role in breast carcinogenesis and that a misbalanced expression of PR isoforms differentially affects breast cancer progressionand antiprogestin treatment responsiveness.Moreover, we have shown, in preclinical and clinical studies, that mifepristone exerts antiproliferative effects in tumors expressing higher levels of PR isoform A (PRA) than B (PRB), named PRA-H, suggesting the necessity to develop methods to identify these patients using non-invasive technologies. Our aim was to compare the proteome profile of PRA-H breast carcinomas with those with the opposite ratio (PRB-H). Nuclear and cytosolic protein fractions were obtained from 18 breast cancer samples classified as PRA-H or PRB-H and were studied by LC-MS/MS (UltiMate 3000 LC system - Q Exactive HF-X mass spectrometer - Thermo). We observed 289 differentially regulated proteins in cytosol (164 down and 125 up) and 301 in nuclear extracts (131 down and 170 up; logFC > 1, pval < 0.05) from both groups. Enrichment analysis showed biological processes related to intracellular transport (FDR = 9.58e-08), metabolic (FDR = 0.0028) and actin filament-based processes (FDR = 1.79e-05) in PRB-H tumors; while in PRA-H tumors, pathways related to oxoacid metabolic (FDR = 0.0015), immune effector (FDR = 1.59e-08) and electron transport chain (FDR = 3.35e-06) processes were enriched. Finally, using the differentially expressed proteins, we studied those that might be secreted. Among them, we found CPB1, whose differential mRNA expression has already been reported in a similar setting in previous assays. This study underscores the biological differences between PRA-H and PRB-H breast carcinomas and provides candidates that might be used as surrogate markers in plasma to identify patients that may benefit from an antiprogestin treatment.
Fil: Elia, Andres Maximiliano. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina
Fil: Sánchez, Jana. Centro Nacional de Investigaciones Oncologicas; España
Fil: Vitorino, Rui. Universidade de Aveiro; Portugal
Fil: Saldain, Leo. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina
Fil: Martínez Vazquez, Paula. Gobierno de la Provincia de Buenos Aires. Hospital Zonal General de Agudos Magdalena Villegas de Martinez.; Argentina
Fil: Burruchaga, Javier. Gobierno de la Provincia de Buenos Aires. Hospital Zonal General de Agudos Magdalena Villegas de Martinez.; Argentina
Fil: Spengler, Eunice. Gobierno de la Provincia de Buenos Aires. Hospital Zonal General de Agudos Magdalena Villegas de Martinez.; Argentina
Fil: Muñoz, Javier. Centro Nacional de Investigaciones Oncologicas; España
Fil: Rojas, Paola Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina
Fil: Helguero, Luisa. Universidade de Aveiro; Portugal
Fil: Lanari, Claudia Lee Malvina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina
LXVII Reunión Anual de la Sociedad Argentina de Investigación Clínica ; LXX Reunión Anual de la Sociedad Argentina de Inmunología & Congreso Franco-Argentino de Inmunología y Reunión Anual 2022 de la Sociedad Argentina de Fisiología
Mar del Plata
Argentina
Sociedad Argentina de Investigación Clínica
Sociedad Argentina de Inmunología
Sociedad Argentina de Fisiología
Materia
PROTEOME
BREAST CANCER
PROGESTERONE RECEPTOR ISOFORM
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/257858
Acceder
id CONICETDig_aab034d94b94d006bf330952dcdb339f
oai_identifier_str oai:ri.conicet.gov.ar:11336/257858
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Characterization of breast tumors with unbalanced levels of progesterone receptor isoforms: a proteomic approachElia, Andres MaximilianoSánchez, JanaVitorino, RuiSaldain, LeoMartínez Vazquez, PaulaBurruchaga, JavierSpengler, EuniceMuñoz, JavierRojas, Paola AndreaHelguero, LuisaLanari, Claudia Lee MalvinaPROTEOMEBREAST CANCERPROGESTERONE RECEPTOR ISOFORMhttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1https://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3It is well established that progesterone receptors (PR) play a relevant role in breast carcinogenesis and that a misbalanced expression of PR isoforms differentially affects breast cancer progressionand antiprogestin treatment responsiveness.Moreover, we have shown, in preclinical and clinical studies, that mifepristone exerts antiproliferative effects in tumors expressing higher levels of PR isoform A (PRA) than B (PRB), named PRA-H, suggesting the necessity to develop methods to identify these patients using non-invasive technologies. Our aim was to compare the proteome profile of PRA-H breast carcinomas with those with the opposite ratio (PRB-H). Nuclear and cytosolic protein fractions were obtained from 18 breast cancer samples classified as PRA-H or PRB-H and were studied by LC-MS/MS (UltiMate 3000 LC system - Q Exactive HF-X mass spectrometer - Thermo). We observed 289 differentially regulated proteins in cytosol (164 down and 125 up) and 301 in nuclear extracts (131 down and 170 up; logFC > 1, pval < 0.05) from both groups. Enrichment analysis showed biological processes related to intracellular transport (FDR = 9.58e-08), metabolic (FDR = 0.0028) and actin filament-based processes (FDR = 1.79e-05) in PRB-H tumors; while in PRA-H tumors, pathways related to oxoacid metabolic (FDR = 0.0015), immune effector (FDR = 1.59e-08) and electron transport chain (FDR = 3.35e-06) processes were enriched. Finally, using the differentially expressed proteins, we studied those that might be secreted. Among them, we found CPB1, whose differential mRNA expression has already been reported in a similar setting in previous assays. This study underscores the biological differences between PRA-H and PRB-H breast carcinomas and provides candidates that might be used as surrogate markers in plasma to identify patients that may benefit from an antiprogestin treatment.Fil: Elia, Andres Maximiliano. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Sánchez, Jana. Centro Nacional de Investigaciones Oncologicas; EspañaFil: Vitorino, Rui. Universidade de Aveiro; PortugalFil: Saldain, Leo. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Martínez Vazquez, Paula. Gobierno de la Provincia de Buenos Aires. Hospital Zonal General de Agudos Magdalena Villegas de Martinez.; ArgentinaFil: Burruchaga, Javier. Gobierno de la Provincia de Buenos Aires. Hospital Zonal General de Agudos Magdalena Villegas de Martinez.; ArgentinaFil: Spengler, Eunice. Gobierno de la Provincia de Buenos Aires. Hospital Zonal General de Agudos Magdalena Villegas de Martinez.; ArgentinaFil: Muñoz, Javier. Centro Nacional de Investigaciones Oncologicas; EspañaFil: Rojas, Paola Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Helguero, Luisa. Universidade de Aveiro; PortugalFil: Lanari, Claudia Lee Malvina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaLXVII Reunión Anual de la Sociedad Argentina de Investigación Clínica ; LXX Reunión Anual de la Sociedad Argentina de Inmunología & Congreso Franco-Argentino de Inmunología y Reunión Anual 2022 de la Sociedad Argentina de FisiologíaMar del PlataArgentinaSociedad Argentina de Investigación ClínicaSociedad Argentina de InmunologíaSociedad Argentina de FisiologíaFundación Revista Medicina2022info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/conferenceObjectReuniónJournalhttp://purl.org/coar/resource_type/c_5794info:ar-repo/semantics/documentoDeConferenciaapplication/pdfapplication/vnd.openxmlformats-officedocument.wordprocessingml.documentapplication/pdfhttp://hdl.handle.net/11336/257858Characterization of breast tumors with unbalanced levels of progesterone receptor isoforms: a proteomic approach; LXVII Reunión Anual de la Sociedad Argentina de Investigación Clínica ; LXX Reunión Anual de la Sociedad Argentina de Inmunología & Congreso Franco-Argentino de Inmunología y Reunión Anual 2022 de la Sociedad Argentina de Fisiología; Mar del Plata; Argentina; 2022; 91-910025-76801669-9106CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://www.medicinabuenosaires.com/PMID/36368022.pdfNacionalinfo:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T09:57:52Zoai:ri.conicet.gov.ar:11336/257858instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-03 09:57:53.218CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Characterization of breast tumors with unbalanced levels of progesterone receptor isoforms: a proteomic approach
title Characterization of breast tumors with unbalanced levels of progesterone receptor isoforms: a proteomic approach
spellingShingle Characterization of breast tumors with unbalanced levels of progesterone receptor isoforms: a proteomic approach
Elia, Andres Maximiliano
PROTEOME
BREAST CANCER
PROGESTERONE RECEPTOR ISOFORM
title_short Characterization of breast tumors with unbalanced levels of progesterone receptor isoforms: a proteomic approach
title_full Characterization of breast tumors with unbalanced levels of progesterone receptor isoforms: a proteomic approach
title_fullStr Characterization of breast tumors with unbalanced levels of progesterone receptor isoforms: a proteomic approach
title_full_unstemmed Characterization of breast tumors with unbalanced levels of progesterone receptor isoforms: a proteomic approach
title_sort Characterization of breast tumors with unbalanced levels of progesterone receptor isoforms: a proteomic approach
dc.creator.none.fl_str_mv Elia, Andres Maximiliano
Sánchez, Jana
Vitorino, Rui
Saldain, Leo
Martínez Vazquez, Paula
Burruchaga, Javier
Spengler, Eunice
Muñoz, Javier
Rojas, Paola Andrea
Helguero, Luisa
Lanari, Claudia Lee Malvina
author Elia, Andres Maximiliano
author_facet Elia, Andres Maximiliano
Sánchez, Jana
Vitorino, Rui
Saldain, Leo
Martínez Vazquez, Paula
Burruchaga, Javier
Spengler, Eunice
Muñoz, Javier
Rojas, Paola Andrea
Helguero, Luisa
Lanari, Claudia Lee Malvina
author_role author
author2 Sánchez, Jana
Vitorino, Rui
Saldain, Leo
Martínez Vazquez, Paula
Burruchaga, Javier
Spengler, Eunice
Muñoz, Javier
Rojas, Paola Andrea
Helguero, Luisa
Lanari, Claudia Lee Malvina
author2_role author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv PROTEOME
BREAST CANCER
PROGESTERONE RECEPTOR ISOFORM
topic PROTEOME
BREAST CANCER
PROGESTERONE RECEPTOR ISOFORM
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv It is well established that progesterone receptors (PR) play a relevant role in breast carcinogenesis and that a misbalanced expression of PR isoforms differentially affects breast cancer progressionand antiprogestin treatment responsiveness.Moreover, we have shown, in preclinical and clinical studies, that mifepristone exerts antiproliferative effects in tumors expressing higher levels of PR isoform A (PRA) than B (PRB), named PRA-H, suggesting the necessity to develop methods to identify these patients using non-invasive technologies. Our aim was to compare the proteome profile of PRA-H breast carcinomas with those with the opposite ratio (PRB-H). Nuclear and cytosolic protein fractions were obtained from 18 breast cancer samples classified as PRA-H or PRB-H and were studied by LC-MS/MS (UltiMate 3000 LC system - Q Exactive HF-X mass spectrometer - Thermo). We observed 289 differentially regulated proteins in cytosol (164 down and 125 up) and 301 in nuclear extracts (131 down and 170 up; logFC > 1, pval < 0.05) from both groups. Enrichment analysis showed biological processes related to intracellular transport (FDR = 9.58e-08), metabolic (FDR = 0.0028) and actin filament-based processes (FDR = 1.79e-05) in PRB-H tumors; while in PRA-H tumors, pathways related to oxoacid metabolic (FDR = 0.0015), immune effector (FDR = 1.59e-08) and electron transport chain (FDR = 3.35e-06) processes were enriched. Finally, using the differentially expressed proteins, we studied those that might be secreted. Among them, we found CPB1, whose differential mRNA expression has already been reported in a similar setting in previous assays. This study underscores the biological differences between PRA-H and PRB-H breast carcinomas and provides candidates that might be used as surrogate markers in plasma to identify patients that may benefit from an antiprogestin treatment.
Fil: Elia, Andres Maximiliano. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina
Fil: Sánchez, Jana. Centro Nacional de Investigaciones Oncologicas; España
Fil: Vitorino, Rui. Universidade de Aveiro; Portugal
Fil: Saldain, Leo. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina
Fil: Martínez Vazquez, Paula. Gobierno de la Provincia de Buenos Aires. Hospital Zonal General de Agudos Magdalena Villegas de Martinez.; Argentina
Fil: Burruchaga, Javier. Gobierno de la Provincia de Buenos Aires. Hospital Zonal General de Agudos Magdalena Villegas de Martinez.; Argentina
Fil: Spengler, Eunice. Gobierno de la Provincia de Buenos Aires. Hospital Zonal General de Agudos Magdalena Villegas de Martinez.; Argentina
Fil: Muñoz, Javier. Centro Nacional de Investigaciones Oncologicas; España
Fil: Rojas, Paola Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina
Fil: Helguero, Luisa. Universidade de Aveiro; Portugal
Fil: Lanari, Claudia Lee Malvina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina
LXVII Reunión Anual de la Sociedad Argentina de Investigación Clínica ; LXX Reunión Anual de la Sociedad Argentina de Inmunología & Congreso Franco-Argentino de Inmunología y Reunión Anual 2022 de la Sociedad Argentina de Fisiología
Mar del Plata
Argentina
Sociedad Argentina de Investigación Clínica
Sociedad Argentina de Inmunología
Sociedad Argentina de Fisiología
description It is well established that progesterone receptors (PR) play a relevant role in breast carcinogenesis and that a misbalanced expression of PR isoforms differentially affects breast cancer progressionand antiprogestin treatment responsiveness.Moreover, we have shown, in preclinical and clinical studies, that mifepristone exerts antiproliferative effects in tumors expressing higher levels of PR isoform A (PRA) than B (PRB), named PRA-H, suggesting the necessity to develop methods to identify these patients using non-invasive technologies. Our aim was to compare the proteome profile of PRA-H breast carcinomas with those with the opposite ratio (PRB-H). Nuclear and cytosolic protein fractions were obtained from 18 breast cancer samples classified as PRA-H or PRB-H and were studied by LC-MS/MS (UltiMate 3000 LC system - Q Exactive HF-X mass spectrometer - Thermo). We observed 289 differentially regulated proteins in cytosol (164 down and 125 up) and 301 in nuclear extracts (131 down and 170 up; logFC > 1, pval < 0.05) from both groups. Enrichment analysis showed biological processes related to intracellular transport (FDR = 9.58e-08), metabolic (FDR = 0.0028) and actin filament-based processes (FDR = 1.79e-05) in PRB-H tumors; while in PRA-H tumors, pathways related to oxoacid metabolic (FDR = 0.0015), immune effector (FDR = 1.59e-08) and electron transport chain (FDR = 3.35e-06) processes were enriched. Finally, using the differentially expressed proteins, we studied those that might be secreted. Among them, we found CPB1, whose differential mRNA expression has already been reported in a similar setting in previous assays. This study underscores the biological differences between PRA-H and PRB-H breast carcinomas and provides candidates that might be used as surrogate markers in plasma to identify patients that may benefit from an antiprogestin treatment.
publishDate 2022
dc.date.none.fl_str_mv 2022
dc.type.none.fl_str_mv info:eu-repo/semantics/publishedVersion
info:eu-repo/semantics/conferenceObject
Reunión
Journal
http://purl.org/coar/resource_type/c_5794
info:ar-repo/semantics/documentoDeConferencia
status_str publishedVersion
format conferenceObject
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/257858
Characterization of breast tumors with unbalanced levels of progesterone receptor isoforms: a proteomic approach; LXVII Reunión Anual de la Sociedad Argentina de Investigación Clínica ; LXX Reunión Anual de la Sociedad Argentina de Inmunología & Congreso Franco-Argentino de Inmunología y Reunión Anual 2022 de la Sociedad Argentina de Fisiología; Mar del Plata; Argentina; 2022; 91-91
0025-7680
1669-9106
CONICET Digital
CONICET
url http://hdl.handle.net/11336/257858
identifier_str_mv Characterization of breast tumors with unbalanced levels of progesterone receptor isoforms: a proteomic approach; LXVII Reunión Anual de la Sociedad Argentina de Investigación Clínica ; LXX Reunión Anual de la Sociedad Argentina de Inmunología & Congreso Franco-Argentino de Inmunología y Reunión Anual 2022 de la Sociedad Argentina de Fisiología; Mar del Plata; Argentina; 2022; 91-91
0025-7680
1669-9106
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/https://www.medicinabuenosaires.com/PMID/36368022.pdf
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
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dc.coverage.none.fl_str_mv Nacional
dc.publisher.none.fl_str_mv Fundación Revista Medicina
publisher.none.fl_str_mv Fundación Revista Medicina
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instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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